Abstract Body (Do not enter title and authors here): Background: Obesity-related heart failure with preserved ejection fraction (HFpEF) is associated with increased concentric remodeling and excessive increases in paracardiac adipose tissue (PAT). PAT is increased in obesity and may exacerbate HFpEF through transduction of systemic and myocardial inflammation. Tirzepatide, a long-acting glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, leads to weight loss and in HFpEF may reduce left ventricular (LV) mass and PAT.
Methods: In the cardiac magnetic resonance imaging (CMR) substudy of the SUMMIT trial, 175 patients with NYHA class II-IV HF, ejection fraction ≥50%, and body mass index ≥30 kg/m2 were randomized to tirzepatide (2.5 mg SQ weekly, increasing to a maximum of 15 mg weekly [N=80]) or placebo (N=95) for 1 year and were imaged at baseline and at the Week 52 visit or early termination (ET) visit if ET was prior to Week 52. CMR included steady state free precession cine imaging in short axis (8 mm thick slices, no gap) covering the heart from the left ventricle (LV) apex through the posterior left atrium (LA) and 3 long-axis orientations. An experienced operator blinded to treatment group used MEDIS software to analyze LV and LA size and function including strain, and paracardiac (sum of epicardial and pericardial) fat volume.
Results: In the overall trial, tirzepatide reduced the combined risk of cardiovascular death or worsening heart failure events and improved health status as compared to placebo. One hundred eleven patients completed the study with adequate image quality for analysis at both time points. Effects of tirzepatide vs placebo on CMR data will be presented, including effects on LV mass, paracardiac fat volume, LV end-diastolic and end-systolic volumes, ejection fraction, LV global circumferential and longitudinal strain, LA end-diastolic and end-systolic volumes and ejection fraction, and LA global circumferential, longitudinal, and radial strain.
Conclusions: The effect of tirzepatide (vs placebo) on cardiac structure and function in patients with obesity-related HFpEF will be presented and evaluated for correlations with clinical efficacy across multiple domains.